A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 6-Week Clinical Study to Assess the Efficacy and Safety of Beclomethasone Dipropionate Delivered Via Breath-Actuated Inhaler (BAI) at 320 or 640 mcg/Day in Adolescent and Adult Patients 12 Years of Age and Older With Persistent Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 713
- 试验地点
- 75
- 主要终点
- Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 6 Weeks (AUEC(0-6wk))
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of beclomethasone dipropionate administered via BAI at a dose strength of 40 or 80 mcg per oral inhalation (320 or 640 mcg/day, respectively) compared with placebo treatment in patients with persistent asthma as assessed by the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) forced expiratory volume in 1 second (FEV1) area under the effect curve from time 0 to 6 weeks (AUEC[0-6wk]).
详细描述
Run-In Period (Days -14 to Day -1): Participants were provided with single-blind placebo breath-actuated inhaler (BAI) or metered-dose inhaler (MDI) device for twice-daily use after appropriate training and demonstration of the proper technique. Participants discontinued their current asthma therapy for the duration of the study.
Treatment Period (Day 0 to Week 6): Participants were randomly assigned to treatment and device type through a qualified randomization service provider (ie, IRT). The interactive response technology (IRT) system stratified patients based on treatment at the time of screening visit, either inhaled corticosteroid (ICS) or non-corticosteroid (NCS). During the study, blinded persons were blinded to treatment (active or placebo) assigned but not device (BAI or MDI) assignment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has a diagnosis of asthma as defined by the NIH. The asthma diagnosis
- •has been present for a minimum of 3 months and has been stable (defined as no exacerbations and no changes in medication) for at least 30 days.
- •The patient has been maintained on stable doses of :
- •non-corticosteroid therapy
- •inhaled corticosteroid therapy
- •Written informed consent/assent is obtained. For adult patients (18 years of age and older, or as applicable per local regulations), the written informed consent form (ICF) must be signed and dated by the patient before conducting any study-related procedure. For minor patients (ages 12 to 17 years, or as applicable per local regulations), the written ICF must be signed and dated by the parent/legal guardian and the written informed assent form must be signed and dated by the patient before conducting any study-related procedure.
- •The patient is a male or female 12 years of age or older as of the visit when informed consent/assent is signed (screening or prescreening visit, as applicable). (Note: Age requirements are as specified or allowed by local regulations.)
- •The patient is able to perform acceptable and repeatable spirometry
- •The patient is able to use an electronic diary after training.
- •The patient is able to use devices properly
- •If female, patient is currently not pregnant, not breast feeding, nor attempting to become pregnant (for 30 days before the screening visit (SV) and throughout the duration of the study and for 30 days after patient's last study visit) or, is of childbearing potential and not sexually active, has a negative urine pregnancy test, and is willing to commit to using a consistent and acceptable method of birth control
- •If male, the patient is willing to commit to an acceptable method of birth control for the duration of the study, is surgically sterile or exclusively has same-sex partner(s).
- •The patient does not have any concomitant conditions or treatments that could interfere with study conduct, influence the interpretation of study observations/results, or put the patient at increased risk during the study as judged by the investigator.
- •The patient/parent/legal guardian is capable of understanding the requirements, risks, and benefits of study participation, and, as judged by the investigator, capable of giving informed consent/assent and being compliant with all study requirements (eg, dose schedules, visit schedules, procedures, and record keeping).
- •The patient, as judged by the investigator, is able to discontinue all asthma medications at the SV.
- •other criteria apply, please contact the investigator for more information
- •Exclusion Criteria
- •Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation and/or associated with hypercapnea, respiratory arrest or hypoxic seizures, asthma-related syncopal episode(s), or hospitalizations within the past year.
- •The patient received systemic corticosteroids within 30 days before the SV (for asthma exacerbation or for other indications).
- •The patient has participated in any investigational drug study as a randomized patient within the 30 days (starting at the final visit of that study) preceding SV (or prescreening visit, as applicable), or plans to participate in another investigational drug study at any time during this study.
- •The patient has previously participated in a beclomethasone dipropionate breath-actuated inhaler (device) (BAI) study as a randomized patient.
- •The patient has a known hypersensitivity to any corticosteroid or any of the excipients in the study drug or rescue medication formulation.
- •The patient has been treated with any known strong cytochrome inhibitors during the study.
- •The patient has been treated with any of the prohibited medications during the prescribed (per protocol) withdrawal periods before the SV.
- •The patient currently smokes or has a smoking history of 10 pack years or more (a pack year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient may not have used tobacco products within the past year (eg, cigarettes, cigars, chewing tobacco, or pipe tobacco).
- •The patient has a suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the SV.
- •The patient has a history of alcohol or drug abuse within 2 years preceding SV.
- •The patient has had an asthma exacerbation requiring oral corticosteroids within 1 month before the SV, or has had any hospitalization for asthma within 3 months before SV.
- •The patient has initiated immunotherapy (administered by any route) less than 90 days before the SV or had a dose escalation of immunotherapy less than 30 days before the SV.
- •The patient is unable to tolerate or unwilling to comply with the required washout periods and withholding of all applicable medications.
- •The patient has untreated oral candidiasis at SV. Patients with clinical visual evidence of oral candidiasis and who agree to receive treatment and comply with appropriate medical monitoring may enter the study.
- •The patient is either an employee or an immediate relative of an employee of the clinical investigational center.
- •A member of the patient's household is participating in the study at the same time. (However, after the enrolled patient completes or discontinues participation in the study, another patient from the same household may be screened).
- •The patient has a disease/condition that, in the medical judgment of the investigator, would put the safety of the patient at risk through participation or that could affect the efficacy or safety analysis if the disease/condition worsened during the study.
- •other criteria apply, please contact the investigator for more information
排除标准
- 未提供
研究组 & 干预措施
Beclomethasone dipropionate BAI 320
Beclomethasone Dipropionate Delivered via Breath-Actuated Inhaler (BAI) at 320 mcg/day (40 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: Beclomethasone dipropionate via 320 mcg BAI (Drug)
Beclomethasone dipropionate BAI 320
Beclomethasone Dipropionate Delivered via Breath-Actuated Inhaler (BAI) at 320 mcg/day (40 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: albuterol/salbutamol (Drug)
Beclomethasone dipropionate BAI 640
Beclomethasone Dipropionate Delivered via Breath-Actuated Inhaler (BAI) at 640 mcg/day (80 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: Beclomethasone Dipropionate 640 (Drug)
Beclomethasone dipropionate BAI 640
Beclomethasone Dipropionate Delivered via Breath-Actuated Inhaler (BAI) at 640 mcg/day (80 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: albuterol/salbutamol (Drug)
Beclomethasone dipropionate MDI 320
Beclomethasone dipropionate Metered Dose Inhaler (MDI) 320 mcg/day (40 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: albuterol/salbutamol (Drug)
Beclomethasone dipropionate MDI 320
Beclomethasone dipropionate Metered Dose Inhaler (MDI) 320 mcg/day (40 mcg/inhalation, 4 inhalations twice daily)
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: Beclomethasone dipropionate via 320 mcg MDI (Drug)
Placebo
Pooled breath-actuated inhaler (BAI) or metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks.
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: Placebo (Drug)
Placebo
Pooled breath-actuated inhaler (BAI) or metered-dose inhaler (MDI) placebo groups. Participants were instructed to take 4 inhalations twice daily for 6 weeks.
Albuterol/salbutamol hydrofluoroalkane (HFA) metered-dose inhaler (MDI) (90 mcg ex-actuator) or equivalent was supplied by the sponsor for use as rescue medication during the run-in and double-blind study periods.
干预措施: albuterol/salbutamol (Drug)
结局指标
主要结局
Standardized Baseline-Adjusted Trough Morning Forced Expiratory Volume in One Minute (FEV1) Area Under the Effect Curve From Time Zero to 6 Weeks (AUEC(0-6wk))
时间窗: Baseline (Day 0 of Treatment Period), weeks 2, 4, 6
The primary efficacy variable was the standardized baseline-adjusted trough morning (pre-dose and pre-rescue bronchodilator) FEV1 AUEC(0-6wk). Pulmonary function measurements such as FEV1 were obtained electronically by spirometry at the randomization visit, each treatment visit (Weeks 2, 4 and 6) and any unscheduled visit (such as the early termination visit). The highest FEV1 value from 3 acceptable and 2 repeatable maneuvers (maximum of 8 attempts) was used. The least-square (LS) means, difference of LS means and its 95% confidence interval (CI), and p-value represent the results obtained from the analysis of covariance with covariate adjustment for baseline, sex, age, current asthma therapy, and treatment.
次要结局
- Participants With Treatment-Emergent Adverse Events (TEAE)(Day 0 to Week 6)
- Change From Baseline in Weekly Average of Daily Trough Morning Peak Expiratory Flow (PEF) Rate Over the 6-Week Treatment Period(Timeframes: Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks)
- Change From Baseline in Weekly Average of Total Daily Asthma Symptom Score Over the 6-Week Treatment Period(Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks)
- Count of Participants Withdrawn From Study Drug Treatment Due to Meeting Stopping Criteria for Worsening Asthma(Day 0 to Week 6)
- Change From Baseline in Weekly Average of Daily Trough Morning Forced Expiratory Volume in One Minute (FEV1) Rate Over the 6-Week Treatment Period(Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks)
- Change From Baseline in Weekly Average of Total Daily (24-Hour) Rescue Medication Use Over the 6-Week Treatment Period(Baseline (Day -7 to Day 0 which is part of the Run-in Period); Treatment Period from Day 0 up to 6 weeks)